1.A Nomogram for Predicting Metachronous Gastric Cancer After Endoscopic Submucosal Dissection of Early Gastric Cancer Following Successful Helicobacter pylori Eradication
Shangtao MAO ; Miao LIU ; Tao ZHAO ; Qiong YAN ; Ying XIANG ; Hai WU ; Wenjun LI ; Hongji TAO ; Duanming ZHUANG ; Lei WANG ; Guifang XU
Journal of Gastric Cancer 2026;26(2):279-294
Purpose:
Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori.
Materials and Methods:
A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection.
Results:
A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively.
Conclusions
Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.
2.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.
3.Clinical application value of three-dimensional visualization technology in the precise diagnosis and treatment of locally advanced differentiated thyroid cancer
Hai YAN ; Jian ZHU ; Dan WANG ; Changrui LIU ; Yixin LIU ; Dongliang ZHAI ; Yuanyuan LIU ; Yuan LI ; Qingqing HE
International Journal of Surgery 2025;52(1):19-27
Objective:To investigate the feasibility and effectiveness of three-dimensional visualization technology in the precise diagnosis and treatment of locally advanced differentiated thyroid cancer(DTC).Methods:A retrospective analysis was conducted on the clinical data of 196 patients with locally advanced DTC treated at the 960th Hospital of the PLA from December 2021 to August 2023. The cohort included 71 male and 125 female patients, with a mean age of 43.7 years (rangd from 18 to 77 years). All patients underwent neck-enhanced CT scans and were divided into two groups: the study group( n=102), which underwent preoperative three-dimensional visualization of CT data, and the control group( n=94), which did not. Baseline data for both groups were matched using SPSS27.0 with 1∶1 propensity score matching (PSM) and the caliper value was 0.02. A total of 49 patients were included in each group, including 35 first-time surgeries and 14 reoperation. Among the 70 first-time surgeries, 29 patients underwent robotic surgery and 41 underwent open surgery. Among the 28 reoperations, 4 underwent robotic surgery and 24 underwent open surgery. In the study group, three-dimensional visual models were used to comprehensively evaluate the tumor and metastatic lesion size, spatial location, and adjacent relationship with surrounding organs, surgical treatments were guided by these models, whereas the control group relied on two-dimensional imaging for guidance. The clinical data were statistically analyzed using SPSS27.0. Results:All operations were successfully completed. There were no statistical differences in baseline data between the two groups( P>0.05). Among first-time surgeries, the study group showed shorter operation times [175(145, 200) min vs 205(182, 249) min, P<0.001], a lower incidence of postoperative chyle leak (0 vs 8.57%, P=0.027), a higher rate of robotic surgery (48.57% vs 34.28%, P=0.225), a greater number of harvested lymph nodes [46(40, 62) vs 37(28, 56), P=0.032], a greater number of cervical lymph node metastasis[15(7, 22) vs 5(1, 14), P=0.004] and a larger diameter of metastasis lymph nodes[12(10, 16) mm vs 4(1, 10) mm, P<0.001]. There were no significant differences in intraoperative blood loss, postoperative drainage days and incidence of hypoparathyroidism( P>0.05). During the reoperation, the study group had shorter operation times[103.5(95.0, 122.5) min vs 146.50(133.25, 172.25) min, P<0.001], less intraoperative blood loss[12.50(8.75, 22.50) mL vs 30.00(17.50, 35.00) mL, P=0.021], fewer postoperative drainage days[5.00(4.00, 6.00) d vs 6.00(5.00, 7.25) d, P=0.016] and a lower incidence of hypoparathyroidism(7.14% vs 42.86%, P=0.038).The robotic surgery rate was higher in the study group (21.42% vs 7.14%, P=0.596). There were no significant differences in lymph node dissection numbers, metastatic lymph node counts, or chyle leak incidences between the two groups ( P>0.05). No acute bleeding or incision infection occurred in any patient postoperatively. Conclusion:Three-dimensional visualization technology is an effective preoperative assessment method for evaluating the resectability of tumors and metastases lesions in locally advanced DTC. It enhances the accuracy and safety of surgery for locally advanced DTC.
4.Prognostic comparison between pulmonary metastasectomy and combination immunotherapy with targeted molecular therapies for advanced hepatocellular carcinoma with pulmonary metastasis:A propensity score matching analysis
Juxian SUN ; Chang LIU ; Xiandong TAO ; Yu YANG ; Hai JIN ; Shuqun CHENG ; Huazheng SHI ; Maolin YAN ; Jie SHI
Liver Research 2025;9(1):29-35
Background and aims:Advanced hepatocellular carcinoma(HCC)with pulmonary metastasis(PM)has a poor prognosis,and optimal treatment strategies remain controversial.This study aimed to compare the long-term outcomes of patients with advanced HCC with PM who were treated with resection of pul-monary metastases versus those treated with targeted therapies combined with immunotherapy.Methods:A retrospective analysis was conducted on the medical records of HCC patients with PM who underwent either pulmonary metastasectomy or immunotherapy combined with targeted therapies at the Eastern Hepatobiliary Surgery Hospital,Changhai Hospital of Shanghai,Fujian Provincial Hospital,and West China Hospital of Sichuan University from September 2013 to October 2022.One-to-one propensity score matching(PSM)was employed to control the influence of potential confounders,and the survival outcomes were compared.Results:A total of 119 HCC patients with PM were included in this study.The overall survival(OS)of patients who underwent pulmonary metastasectomy was significantly longer than that of patients who received immunotherapy targeted combinations(OS:1-year,80.0%vs.59.3%;2-year,31.7%vs.20.3%;3-year,20.0%vs.0;P<0.001).After PSM,the long-term prognosis of the pulmonary metastasectomy group remained significantly better than that of the immunotherapy combination group(OS:1-year,87.0%vs.69.6%;2-year,34.8%vs.30.4%;3-year,21.7%vs.0;P=0.005).Multivariate analysis revealed that treat-ment allocation(hazard ratio(HR)=2.177,95%confidence interval(CI)=1.068-4.439)and hepatic tumor T stage(HR=2.342,95%CI=1.209-4.538)were independent risk factors for OS.Conclusions:Pulmonary metastasectomy was associated with improved survival compared to immu-notherapy combined with targeted therapies and may represent an optimal treatment option for highly selected HCC patients with resectable PM.
5.Effect of downregulating Hsa-circ-0101216 expression on gemcitabine chemoresistance in pancreatic cancer and its mechanism
Hai-Chao LIU ; Shao-Peng LIU ; Hong-Xian YAN ; Ming-Hui BAI ; Ji-Xiang ZHANG ; Ying-Bo LI ; Chuang WANG ; Kai ZOU
Medical Journal of Chinese People's Liberation Army 2025;50(6):656-664
Objective To analyze the effect of Hsa-circ-0101216 on gemcitabine(GEM)chemotherapy resistance in pancreatic cancer and its mechanism.Methods Differentially expressed circRNAs between GEM-resistant pancreatic cancer cells and parent cells were screened using the GEO database.Pancreatic cancer GEM resistant cell lines(BxPC-3-GEM and Capan-1-GEM)were constructed by intermittent concentration gradient method.qRT-PCR was used to detect the expression of Hsa-circ-0101216 in cells.GEM resistant pancreatic cancer cell lines were taken and divided into sh-circ-0101216 group(knockdown of circ-0101216),sh-NC group(transfected with sh-NC),and blank control group(untreated).CCK-8 assay and EdU proliferation assay were used to detect the half inhibitory concentration(IC50)of GEM and proliferation ability of cells in each group.Western blotting was performed to detect the expression of multidrug resistance-related protein 1(MRP1),breast cancer resistance protein(BCRP),and human equilibrative nucleoside transporter-1(hENT-1).A subcutaneous xenograft tumor model of human pancreatic cancer in nude mice was constructed,and sh-NC+GEM group and sh-circ-0101216+GEM group(n=6)were set up.The volume and weight of xenograft tumor in nude mice were compared between the two groups.Western blotting and immunohistochemistry were used to detect the expression of MRP1,BCRP,and hENT-1 proteins in xenograft tumor tissues,and EDU proliferation assay was used to detect the proliferation ability of tumor cells.Results The GEO database screening showed that Hsa-circ-0101216 was up-regulated in GEM-resistant pancreatic cancer cell lines.Pancreatic cancer GEM-resistant cell lines were successfully constructed,and the expression levels of Hsa-circ-0101216 and the IC50 value in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly higher than those in parental cells(P<0.05).In sh-circ-0101216 group,the IC50 values of GEM,cell viability,EdU positivity rate,and the expression levels of MRP1 and BCRP proteins in GEM-resistant pancreatic cancer cells BxPC-3-GEM and Capan-1-GEM were significantly lower than those in blank control group and sh-NC group,while the expression level of hENT-1 protein was significantly higher(P<0.05 or P<0.001).In sh-circ-0101216+GEM group,the weight and volume of subcutaneous xenograft tumors in nude mice,the expression levels and positive expression rates of MRP1 and BCRP proteins in tumor tissues,and the EdU positive rate were significantly lower than those in sh-NC+GEM group,while the expression level and positive expression rate of hENT-1 protein were significantly higher(P<0.05).Conclusions Hsa-circ-0101216 is highly expressed in GEM-resistant pancreatic cancer cell lines.Its knockdown can inhibit the proliferation of pancreatic cancer cells and enhance the chemosensitivity of pancreatic cancer cells to GEM.The mechanism may be related to the regulation of transmembrane transporter protein expression.
6.Establishment and evaluation of a predictive model for spontaneous peritonitis in HBV-related primary liver cancer
Hong-Yan WEI ; Yong-Zhen CHEN ; Ren-Hai TIAN ; Li-Xian CHANG ; Ying-Yuan ZHANG ; Dan-Qing XU ; Chun-Yun LIU ; Li LIU
Medical Journal of Chinese People's Liberation Army 2025;50(8):949-957
Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P<0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95%CI 3.271-10.213,P<0.001;Grade C:OR=14.818,95%CI 7.697-28.526,P<0.001),PVTT(OR=2.893,95%CI 2.037-4.108,P<0.001),WBC(OR=1.088,95%CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95%CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.
7.Molecular mechanism of verbascoside in promoting acetylcholine release of neurotransmitter.
Zhi-Hua ZHOU ; Hai-Yan XING ; Yan LIANG ; Jie GAO ; Yang LIU ; Ting ZHANG ; Li ZHU ; Jia-Long QIAN ; Chuan ZHOU ; Gang LI
China Journal of Chinese Materia Medica 2025;50(2):335-348
The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals
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Rats
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Glucosides/administration & dosage*
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Acetylcholine/metabolism*
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Alzheimer Disease/genetics*
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PC12 Cells
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Phenols/chemistry*
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Neurotransmitter Agents/metabolism*
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Drugs, Chinese Herbal
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Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics*
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Humans
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Phosphorylation/drug effects*
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Calcium/metabolism*
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Polyphenols
8.Mechanism of tannins from Galla chinensis cream in promoting skin wound healing in rats based on FAK/PI3K/Akt/mTOR signaling pathway.
Wen YI ; Zi-Yi YAN ; Meng-Qiong SHI ; Ying ZHANG ; Jie LIU ; Qian YI ; Hai-Ming TANG ; Yi-Wen LIU
China Journal of Chinese Materia Medica 2025;50(2):480-497
This study investigated the effects and action mechanism of tannins from Galla chinensis cream(TGCC) on the skin wound of rat tail. Male Sprague Dawley(SD) rats were randomly divided into a control group, model group, model+low-dose TGCC(50 mg per rat) group, model+high-dose TGCC group(100 mg per rat), and model+TGC+FAK inhibitor(Y15) cream(100 mg+10 mg per rat) group, with 10 rats in each group. After the rat tail skin injury model was successfully constructed, in the treatment group, corresponding drugs were applied to the wound surface, while in the control and model groups, the same amount of cream base as the TGCC group was applied by the same method. Then, sterile gauze was wrapped around the wound edge, and these operations were performed three times a day for 28 consecutive days. The wound healing status at the third, seventh, eleventh, fourteenth, twenty-first, and twenty-eighth days was recorded, and the wound healing rate and healing time were calculated. On the day after the last dose of medication, rat serum and tail skin wound tissue were collected for analyzing the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(CREA), urea, reactive oxygen species(ROS), interferon gamma(IFN-γ), interleukin(IL)-1β, IL-6, IL-4, IL-10, tumor necrosis factor(TNF)-α, as well as catalase(CAT), glutathione(GSH), lactate dehydrogenase(LDH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC), platelet endothelial cell adhesion molecule-1(CD31), and leukocyte differentiation antigen 34(CD34) in the wound tissue of rat tail skin. Hematoxylin-eosin, Masson, and sirius red staining were used to observe the morphological changes in the wound tissue of rat tail skin. The thickness of the epidermis, the number of fibroblasts and blood vessels, and the contents of collagen fibers, typeⅠ collagen(COLⅠ), and COLⅢ were calculated. The mRNA expressions of keratin 10(KRT10), KRT14, vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), epidermal growth factor(EGF), CD31, CD34, matrix metallopeptidase-2(MMP-2), MMP-9, COLⅠ, COLⅢ, desmin, fibroblast specific protein 1(FSP1), IFN-γ, IL-1β, TNF-α, IL-4, IL-6, and IL-10 in skin wound tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expressions of KRT10, KRT14, VEGF, FGF, EGF, MMP-2, MMP-9, COLⅠ, COLⅢ, desmin, FSP1, focal adhesion kinase(FAK), phosphorylated focal adhesion kinase(p-FAK), phosphatidylin-ositol-3-kinase(PI3K), phosphorylated phosphatidylin-ositol-3-kinase(p-PI3K), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results manifest that TGCC can dramatically elevate the healing rate of rat tail wounds and shorten wound healing time. Besides, it can reduce serum ROS levels, the contents of MDA, MPO, and LDH in the rat skin wound tissue, as well as the serum IFN-γ, IL-1β, IL-6, and TNF-α levels and the mRNA expression levels of IFN-γ, IL-1β, IL-6, and TNF-α in the skin wound tissue. It can elevate the activities of CAT, GSH, SOD, and T-AOC in wound tissue, the IL-4 and IL-10 contents in serum, and the mRNA expressions of IL-4 and IL-10 in the wound tissue. In addition, TGGC can inhibit inflammatory cell infiltration and increase the epidermal thickness, counts of fibroblasts and blood vessels, and contents of collagen fibers, COLⅠ, and COLⅢ. Besides, TGCC can elevate the mRNA and protein expressions of epidermal differentiation markers(KRT10 and KRT14), endothelial cell markers(CD31 and CD34), angiogenesis and fibroblast proliferation, differentiation markers(VEGF, FGF, EGF, COLⅠ, COLⅢ, desmin, and FSP1), reduce the mRNA and protein expressions of gelatinases(MMP-2 and MMP-9), and increase protein expressions of p-FAK, p-PI3K, p-Akt, p-mTOR, as well as ratios of p-FAK/FAK, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. These results suggest that TGCC can significantly facilitate skin wound healing, and its mechanism may be related to the activation of the FAK/PI3K/Akt/mTOR signaling pathway, inhibition of inflammatory cell infiltration in skin wound tissue, elevation of epidermal thickness, counts of fibroblasts and vessels, and contents of collagen fiber, COLⅠ, and COLⅢ, and reduction of MMP-2 and MMP-9 expressions, thus accelerating wound healing.
Animals
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Male
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Wound Healing/drug effects*
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Rats
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Rats, Sprague-Dawley
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Signal Transduction/drug effects*
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TOR Serine-Threonine Kinases/genetics*
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Phosphatidylinositol 3-Kinases/genetics*
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Skin/metabolism*
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Proto-Oncogene Proteins c-akt/genetics*
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Tannins/pharmacology*
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Humans
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Drugs, Chinese Herbal/administration & dosage*
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Focal Adhesion Kinase 1/genetics*
9.Material basis of toad oil and its pharmacodynamic effect in a mouse model of atopic dermatitis.
Yu-Yang LIU ; Xin-Wei YAN ; Bao-Lin BIAN ; Yao-Hua DING ; Xiao-Lu WEI ; Meng-Yao TIAN ; Wei WANG ; Hai-Yu ZHAO ; Yan-Yan ZHOU ; Hong-Jie WANG ; Ying YANG ; Nan SI
China Journal of Chinese Materia Medica 2025;50(1):165-177
This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals
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Dermatitis, Atopic/immunology*
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Disease Models, Animal
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Mice
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Male
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Gas Chromatography-Mass Spectrometry
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Humans
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Bufonidae
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Oils/administration & dosage*
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Chromatography, High Pressure Liquid
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Female
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Mice, Inbred BALB C
10.Effect of Yuxuebi Tablets on mice with inflammatory pain based on GPR37-mediated inflammation resolution.
Ying LIU ; Guo-Xin ZHANG ; Xue-Min YAO ; Wen-Li WANG ; Ao-Qing HUANG ; Hai-Ping WANG ; Chun-Yan ZHU ; Na LIN
China Journal of Chinese Materia Medica 2025;50(1):178-186
In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics*
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Pain/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Animals
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Mice
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Freund's Adjuvant/pharmacology*
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Ibuprofen
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Pain Threshold/drug effects*
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Hyperalgesia/genetics*
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Ganglia, Spinal
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Interleukin-10/genetics*
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Transforming Growth Factor beta/genetics*
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Reverse Transcriptase Polymerase Chain Reaction
;
Tablets
;
Receptors, G-Protein-Coupled

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